Microfluidic devices (microdevices) hold great promise for many applications, particularly in applications that employ rare or expensive fluids. Proteomics and genomics are two important areas in which microfluidic devices may be employed. For example, many of the best-selling drugs today either are proteins or act by targeting proteins. In addition, many molecular markers of disease, the basis of diagnostics, are peptidic or nucleotidic sequences. Thus, development effort to advance the diagnostics or pharmaceutical technologies has focused on the discovery of medically important proteins and the genes from which they derive. Thus, biomolecular identification is a particularly important aspect of proteomics and genomics.
Biomolecular identification often involves separation processes such as chromatography and mass spectrometry. For example, U.S. Pat. No. 5,705,813 to Apffel et al. describes an integrated planar liquid handling system for matrix-assisted laser-desorption ionization time-of-flight (MALDI-TOF) mass spectrometry. The patent discloses that a reservoir for receiving fluid substances may be interconnected by a microchannel to a MALDI ionization surface, wherein the microchannel comprises a separation region that may be used for chromatographic-type separations.
This approach represents an example of recent progress in microdevices that can be used, for example, as chemical analysis tools or clinical diagnostic tools. The small size of microdevices allows for the analysis of minute quantities of sample, which is an important advantage when the sample is expensive or difficult to obtain. See, e.g., U.S. Pat. No. 5,500,071 to Kaltenbach et al., U.S. Pat. No. 5,571,410 to Swedberg et al., and U.S. Pat. No. 5,645,702 to Witt et al. Sample preparation, separation and detection compartments have been proposed to be integrated on such devices. Because microfabricated devices have a relatively simple construction, they are in theory inexpensive to manufacture. Nevertheless, the production of such devices presents various challenges. For example, the flow characteristics of fluids in the small flow channels of a microfabricated device may differ from the flow characteristics of fluids in larger devices, as surface effects come to predominate and regions of bulk flow become proportionately smaller. Thus, means for producing a motive force that moves analytes and fluids may have to be incorporated into such microanalytical devices. This may involve forming motive force means such as electrodes, which may add to the cost of the microdevice.
Thus, flow control is an important aspect of microdevice technology. Since it is well known that the flow characteristics of fluids in the small flow channels of a microdevice differ greatly from flow characteristics of fluids in bulk, conventional wisdom dictates that valve structures that control flow of fluids in bulk are not easily adapted for use in microfluidic devices. Accordingly, a number of patents disclose various valve technologies employed in microdevices. U.S. Pat. No. 4,869,282 to Sittler et al., for example, discloses a micromachined valve that employs a control force to deflect a polyimide film diaphragm. Similarly, U.S. Pat. Nos. 5,771,902 and 5,819,794 to Lee et al. describe a microvalve that employs a controllable cantilever to direct blood flow. U.S. Pat. No. 5,417,235 to Wise et al describes an integrated microvalve structure with monolithic microflow controller that controls actuation electrostatically, and U.S. Pat. No. 5,368,704 to Madou et al. describes a micromachined valve that can be opened and closed electrochemically. Other aspects of valve operation and control are described in U.S. Pat. Nos. 5,333,831, 5,417,235, 5,725,017, 5,964,239, 5,927,325 and 6,102,068. Many of these valves are complex in construction and are incapable of the fast response times required in certain biomolecule analysis applications due to an excess of “dead space,” i.e., unused and unnecessary space within the microdevice.
Thus, there is a need for an improved and simplified valve structure for controlling fluid flow in microdevices without introducing excessive dead space therein.